Our overall research program is directed to an understanding of the role of proteolipid protein in the development, maintenance and function of CNS myelin. The proteolipid protein is quantitatively the major protein of CNS myelin and consequently its contribution should be considered in autoimmune phenomena involving the nervous system. Our fundamental hypothesis is that, in demyelinating diseases, the immune response involves multiple myelin components and that one of these components is the proteolipid protein. Although myelin basic protein is the principal antigen in the production of acute EAE, other antigens may participate, either directly or indirectly, both in the acute and chronic forms of the disease and in multiple sclerosis. To explore our hypothesis, the specific aims during the next grant period are: A. to study changes in immune cell populations during the development of disease produced by challenge with proteolipid apoprotein. Monoclonal antibodies to T-cells, IgM-bearing B-cells, and Ia antigens will be used to compare (a) peripheral blood lymphocyte populations, analyzed by flow cytometry, with (b) the number and distribution of these populations in brain and spinal cord sections. The analysis will give quantitative data in two species (rabbits and guinea pigs) for comparison of the dynamics of the immune response to proteolipid with that in other forms of EAE. B. to test whether apoprotein modulates immune challenge by other tissue components in experiments on apoprotein-sensitized animals subsequently challenged with other tissue components, and in adoptive transfer experiments. C. to analyze sera and CSF from patients with MS and other demyelinating disorders for proteolipid and anti-proteolipid antibodies. The major purpose or our experimental approach is to provide a broader view of overall events in different EAE models, as a means of contributing to the understanding of immunopathologic patterns in multiple sclerosis.